The goal of this proposal is to develop a peri-transplant brief treatment protocol, using selective lymphoid irradiation, which will result in 1) donor-specific prolonged graft survival; 2) reduction of, or avoidance of, standard immunosuppressants post-grafting; 3) retention of host immunocompetence to other antigens; and 4) clarification of mechanisms of immunosuppression by selective lymphoid irradiation. We will investigate a new approach to allograft prolongation: peri-transplant selective lymphoid irradiation using palladium-hematoporphyrin. This will be combined with standard immunosuppressants (esp. ALS) and used as an acute transient method of recipient immunosuppression in the peri-transplant period to permit immune recovery without graft rejection. Heart transplantation in inbred rats will be the test model to investigate the efficacy of the optimal regimens and the mechanisms involved. Cellular in vivo transfer experiments and in vitro studies of cellular and humoral changes consequent to treatment are proposed to explain and optimize graft prolongation. The proposed approach has been tested in pilot studies in allografts and xenografts and may have major clinical applicability in transplantation because of low toxicity to the host and its ability to facilitate induction of partial tolerance by a short-term treatment of the adult host.